Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome

Abstract

Placental Protein 13 (PP13) is a galectin expressed by the syncytiotrophoblast. Women who subsequently develop preterm preeclampsia have low first trimester maternal serum PP13 concentrations. This study revealed that third trimester maternal serum PP13 concentration increased with gestational age in normal pregnancies (p<0.0001), and it was significantly higher in women presenting with preterm preeclampsia (p=0.02) and HELLP syndrome (p=0.01) than in preterm controls. Conversely, placental PP13 mRNA (p=0.03) and protein, as well as cytoplasmic PP13 staining of the syncytiotrophoblast (p<0.05) was decreased in these pathological pregnancies compared to controls. No differences in placental expression and serum concentrations of PP13 were found at term between patients with preeclampsia and control women. In contrast, the immunoreactivity of the syncytiotrophoblast microvillous membrane was stronger in both term and preterm preeclampsia and HELLP syndrome than in controls. Moreover, large syncytial cytoplasm protrusions, membrane blebs and shed microparticles strongly stained for PP13 in preeclampsia and HELLP syndrome. In conclusion, parallel to its decreased placental expression, an augmented membrane shedding of PP13 contributes to the increased third trimester maternal serum PP13 concentrations in women with preterm preeclampsia and HELLP syndrome.

First trimester screening of maternal placental protein 13 for predicting preeclampsia and small for gestational age: In-house study and systematic review

“…[30] Detection of PP13 may also be variable based on amounts bound to carbohydrates and/or Immunoglobulin E (IgE) bound which could limit access of the antibodies in the assay platform to the antigenic site. Similarly, if the PP13 was shed in syncytiotrophoblast membranes or placental exosomes [31] it may not be as readily measurable as a unbound dimeric protein.…”

Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy

“…Than et al [66] found reduced PP13 mRNA levels in placentas obtained from patients with preeclampsia and HELLP syndrome in the first trimester compared to controls. Blood levels of PP13 mRNA were also significantly lower in preeclampsia compared to controls [67] .…”

A primate subfamily of galectins expressed at the maternal–fetal interface that promote immune cell death

“…Low placental expression and truncation of galectin-13 because of polymorphisms in patients with preeclampsia suggests that altered function of the cluster galectins may be associated with adverse pregnancy outcome (20,21,43).…”

“…The strong selective forces acting on these galectin genes in anthropoids results in a rapid birth and death process, in which genes are lost and gained. Of importance, galectin-13 has decreased placental expression and maternal serum concentrations in the first trimester in women who subsequently develop preeclampsia (20,21,43), a pregnancy-specific syndrome linked to immune maladaptation (2-4, 7, 22). We propose that the immunosuppressive properties of placental galectins in the Chr19 cluster confer additional mechanisms of maternal-fetal immune tolerance, which were necessary for sustaining hemochorial placentation during the long gestation of anthropoid primates.…”

“…They function through transmembrane signaling and the regulation of adaptive and innate immune responses (12)(13)(14)(15). Galectin-1 and galectin-13 (PP13) are also present on the syncytiotrophoblast apical membrane, and their placental expression is altered in preeclampsia (16)(17)(18)(19)(20)(21), a syndrome linked to immune maladaptation (2-4, 7, 22). Other galectins (-3, -9, -14) are also expressed at the maternal-fetal interface (16,18,23,24); many induce the apoptosis of activated T cells and other leukocytes, thereby conferring immune tolerance (25)(26)(27).…”